Phase 1 study of telisotuzumab vedotin in Japanese patients with advanced solid tumors.

Abstract

Telisotuzumab vedotin (formerly ABBV-399) is an antibody-drug conjugate targeting c-Met-overexpressing tumor cells, irrespective of MET gene amplification status. Safety, pharmacokinetics, and preliminary efficacy of telisotuzumab vedotin were evaluated outside of Japan. This phase 1 open-label study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of telisotuzumab vedotin in Japanese patients with advanced solid tumors. Telisotuzumab vedotin was administered intravenously at either 2.4 mg/kg (n = 3) or 2.7 mg/kg (n = 6) every 3 weeks, following a 3 + 3 design. Maximum tolerated dose was not reached on the basis of the study design; no dose-limiting toxicity events were observed. The most common treatment-emergent adverse events related to telisotuzumab vedotin were peripheral sensory neuropathy (44%), and nausea, decreased appetite, and decreased white blood cell count (33% each). Most frequent grade ≥3 treatment-emergent adverse events, irrespective of relationship to telisotuzumab vedotin, were decreased neutrophil count and hypoalbuminemia, reported in two patients (22%) each. Systemic exposure of telisotuzumab vedotin at both dose levels was approximately dose proportional. Pharmacokinetic profile in Japanese patients was similar to that previously reported in non-Japanese patients. Two (22%) patients achieved a partial response, six (67%) had stable disease, one (11%) had progressive disease. Overall disease control rate was 89% (eight of nine patients; 95% confidence interval: 51.8%-99.7%]). Median progression-free survival was 7.1 months (95% confidence interval: 1.2-10.4). In conclusion, telisotuzumab vedotin demonstrated a manageable safety profile, with antitumor activity in Japanese patients with advanced solid tumors; the recommended phase 2 dose was confirmed as 2.7 mg/kg every 3 weeks. ClinicalTrials.gov registration number: NCT03311477.

• Authors: Yutaka Fujiwara, Hirotsugu Kenmotsu, Noboru Yamamoto, Toshio Shimizu, Kan Yonemori, Christopher Ocampo, Apurvasena Parikh, Sumiko Okubo, Kazuteru Fukasawa, Haruyasu Murakami
• Journal: Cancer medicine (Cancer Med) Vol. 10 Issue 7 Pg. 2350-2358 (04 2021) ISSN: 2045-7634 [Electronic] United States
• PMID: 33675179 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal
• Immunoconjugates
• telisotuzumab vedotin

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics)
• Confidence Intervals
• Drug Administration Schedule
• Feeding and Eating Disorders (chemically induced)
• Female
• Humans
• Immunoconjugates (administration & dosage, adverse effects, pharmacokinetics)
• Japan
• Leukopenia (etiology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Nausea (etiology)
• Neoplasms (therapy)
• Peripheral Nervous System Diseases (etiology)
• Progression-Free Survival